The overall goal of the National Center of Image-guided Therapy (NCIGT) is to develop novel tumor localization and targeting technologies for achieving complete resection or focal ablation of cancer with preservation of structure and function of adjacent normal tissues. We will achieve this by improving tumor characterization with accurate definition of its margin, localization and targeting of diseased tissue, and using image guidance technologies to optimize surgical and interventional treatments for improving outcomes and decreasing complications by reducing adjacent tissue damage. We have four TR&Ds: The Prostate TR&D will develop novel platforms to allow for molecular profiling of prostate cancer and imaging to allow for improved predictive markers for guiding biopsy and focal therapy, and by use of image processing methods for monitoring treatment effect. The Neurosurgery TR&D will use a molecular biomarker, mass spectrometry, for intraoperative surgical decision making to better define tumor extent. Advanced functional mapping using fMRI+DTI will be used for individualized treatment planning. The Computation TR&D will develop specialized multimodal image registration algorithms and custom hardware for motion compensation to improve tumor localization and functional mapping. The Guidance TR&D will develop novel instrument and tumor tracking technologies to accurately deliver therapy despite significant physiological motion and tissue deformation. The proposed Image-Guided Therapy methods that introduce new ways to visualize images, guide procedures, and track changes will be integrated with our open source software platform, 3D Slicer.